Human ornithine decarboxylase (ODC) is a well-known oncogene, and the discovery of ODC enzyme inhibitors is a beneficial strategy for cancer therapy and prevention.
We examined the inhibitory effects of a variety of flavone and flavonol derivatives on ODC enzymatic activity, and performed in silico molecular docking of baicalein, 7,8-dihydroxyflavone and myricetin to the whole dimer of human ODC to investigate the possible binding site of these compounds on ODC. We also examined the cytotoxic effects of these compounds with cell-based studies.
Baicalein, 7,8-dihydroxyflavone and myricetin exhibited significant ODC suppression activity with IC
values of 0.88 µM, 2.54 µM, and 7.3 µM, respectively, which were much lower than that of the active-site irreversible inhibitor α-DL-difluoromethylornithine (IC
, the half maximal inhibitory concentration, of approximately 100 µM). Mitapivat ic50 Kinetic studies and molecular docking simulations suggested that baicalein, and 7,8-dihydroxyflavone act as noncompetitive inhibitors that are hydrogen-bonded to the region near the active site pocket in the dimer interface of the enzyme. Baicalein and myricetin suppress cell growth and induce cellular apoptosis, and both of these compounds suppress the ODC-evoked anti-apoptosis of cells.
Therefore, we suggest that the flavone or flavonol derivatives baicalein, 7,8-dihydroxyflavone, and myricetin are potent chemopreventive and chemotherapeutic agents that target ODC.
Therefore, we suggest that the flavone or flavonol derivatives baicalein, 7,8-dihydroxyflavone, and myricetin are potent chemopreventive and chemotherapeutic agents that target ODC.Adolescent sexting is a serious public health concern and is associated with adverse psychosocial outcomes, including depression, anxiety, low self-esteem, declining academic performance, and health problems. Effective prevention of sexting requires a comprehensive and deep understanding of the multiple contexts whereby sexting is likely to occur. The present study explores individual and contextual risk and protective factors that are associated with sexting behavior among a large sample of adolescents. Participants were high school students in midwestern U.S. (N = 2501; LGB n = 309, 76.4% female; non-LGB n = 2192, 47.4% female) who completed self-report measures of sexting and risk (e.g., pornography exposure, impulsivity) and protective (e.g., social support) factors. Path analysis models were conducted with the sexting outcome for groups of LGB and non-LGB students. Among LGB students, results indicated a significant association between sexting and parental monitoring (b = -0.08, p less then 0.01); pornography exposure (b = 0.13, p less then 0.05); dating partners (b = 0.01, p less then 0.01); bullying perpetration (b = 0.17, p less then 0.001); and delinquency (b = 0.13; p less then 0.001). Among non-LGB students, significant associations were found between sexting and alcohol/substance use (b = 0.05, p less then 0.001); bullying (b = 0.08, p less then 0.001); and delinquency (b = 0.06, p less then 0.001). Moderation analyses suggest that parental monitoring may have a buffering effect between sexting and several risk factors. Recommendations for practitioners include considering the protective factors of sexting perpetration and encouraging appropriate levels of parental monitoring and the continued importance of bullying and alcohol and drug prevention programming to decrease risk factors of sexting perpetration.Multiple-color reflectors using bichiral liquid crystal polymer films (BLCPFs) are investigated. The BLCPFs consist of alternate layers of two different single-pitch cholesteric liquid crystal (CLC) layers, named CLC#A and CLC#B. The thickness of each CLC layer equals its single pitch length. The optical properties in terms of reflections, reflection-wavelength ranges, and distributions of reflection spectra of the BLCPFs that result from the fixed pitch length of CLC#A along with the decrease of the pitch length of CLC#B are qualitatively simulated and investigated. The results indicate that the above optical properties of the BLCPFs depend on the LC birefringence and pitch lengths of CLC#A and CLC#B layers. The concept of fabrication method of the BLCPFs by using polymerizable CLCs and thin films of poly(vinylalcohol) or photoalignment materials is discussed. They have potential practical applications in functional color filters, asymmetrical transmission systems, etc., owing to the multiple reflection bands of BLCPFs. Moreover, the BLCPFs, which can enhance the color gamut and light-utilization efficiency of light sources/LC displays, are reported herein.Fish are a convenient model for the study of reparative and post-traumatic processes of central nervous system (CNS) recovery, because the formation of new cells in their CNS continues throughout life. After a traumatic injury to the cerebellum of juvenile masu salmon, Oncorhynchus masou, the cell composition of the neurogenic zones containing neural stem cells (NSCs)/neural progenitor cells (NPCs) in the acute period (two days post-injury) changes. The presence of neuroepithelial (NE) and radial glial (RG) neuronal precursors located in the dorsal, lateral, and basal zones of the cerebellar body was shown by the immunohistochemical (IHC) labeling of glutamine synthetase (GS). Progenitors of both types are sources of neurons in the cerebellum of juvenile O. masou during constitutive growth, thus, playing an important role in CNS homeostasis and neuronal plasticity during ontogenesis. Precursors with the RG phenotype were found in the same regions of the molecular layer as part of heterogeneous constitutive nemals and decreases in the acute post-traumatic period. A study of distribution of cystathionine β-synthase (CBS) in the cerebellum of intact young O. masou showed the expression of the marker mainly in type 1 cells, corresponding to NSCs/NCPs for other molecular markers. In the post-traumatic period, the number of CBS+ cells sharply increased, which indicates the involvement of H2S in the post-traumatic response. Induction of CBS in type 3 cells indicates the involvement of H2S in the metabolism of extracellular glutamate in the cerebellum, a decrease in the production of reactive oxygen species, and also arrest of the oxidative stress development, a weakening of the toxic effects of glutamate, and a reduction in excitotoxicity. The obtained results allow us to consider H2S as a biologically active substance, the numerous known effects of which can be supplemented by participation in the processes of constitutive neurogenesis and neuronal regeneration.Mitapivat ic50
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